Air blast overpressure-induced oxidative stress in rat lungs:
interplay between hemoglobin, antioxidants and lipid
peroxidation.
Gorbunov, Nikolai V., Nabil M. Elsayed, Elena R. Kisin, Andrey V.
Kozlov, and Valerian E. Kagan.
Department of Respiratory Research, Division of Medicine, Walter
Reed Army Institute of Research, Washington, DC 20307, Department of
Environmental and Occupational Health, University of Pittsburgh,
Pittsburgh, PA 15238, Department of Environmental and Occupational
Health Sciences, University of California, Los Angeles, Los Angeles,
CA 90024
APStracts 3:0176L, 1996.
Blast overpressure (BOP) is a phenomenon that describes the
instantaneous rise in atmospheric pressure above ambient resulting
from firing of large caliber weapons or from military and civilian
explosions. Exposure to BOP results in injury to the gas filled
organs such as the lungs which exhibit a contusion-type injury. We
examined the effects of BOP in rats at 5 and 60 min after exposure to
a low-level BOP (62+/-3 kPa). The exposure was found to cause
oxidative stress in the lung that was characterized by: (i) 3.5-fold
decrease in total antioxidant reserves, (ii) depletion of major
water-soluble antioxidants, ascorbate and GSH by 50% and 75%
respectively, (iii) depletion of lipid-soluble antioxidant vitamin E
by 30%, (iv) a 2.5-fold increase of fluorescent end-products of lipid
peroxidation, and (v) increased methemoglobin (metHb) content, at 60
min after exposure. To elucidate the role of released hemoglobin in
blast-induced oxidative stress, we studied the interactions of oxyHb,
metHb, and oxoferrylHb free radical species with two physiologically
important reductants, ascorbate and glutathione (GSH). We found that
both ascorbate and GSH were able to convert oxyHb to metHb in a
reaction that yielded the one-electron oxidation intermediates
semidehydroascorbyl radical and glutathionyl radical, respectively.
This reaction did not occur under anaerobic conditions suggesting
that oxyHb-bound oxygen acted as the electron acceptor. OxyHb induced
peroxidation of cis-parinaric acid in the presence but not absence of
ascorbate or GSH. Thus, the prooxidant action of water-soluble
antioxidants via redox-cycling of oxyHb and metHb may promote
oxidative stress rather than prevent it.
Received 1 November 1995; accepted in final form 2 October 1996.
APS Manuscript Number L313-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996